Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models. Blood advances Alig, S. n., Jurinovic, V. n., Shahrokh Esfahani, M. n., Haebe, S. n., Passerini, V. n., Hellmuth, J. C., Gaitzsch, E. n., Keay, W. n., Tahiri, N. n., Zoellner, A. n., Rosenwald, A. n., Klapper, W. n., Stein, H. n., Feller, A. n., Ott, G. n., Staiger, A. M., Horn, H. n., Hansmann, M. L., Pott, C. n., Unterhalt, M. n., Schmidt, C. n., Dreyling, M. n., Alizadeh, A. A., Hiddemann, W. n., Hoster, E. n., Weigert, O. n. 2020; 4 (18): 4451–62

Abstract

High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is an effective salvage treatment for eligible patients with follicular lymphoma (FL) and early progression of disease (POD). Since the introduction of rituximab, HDT/ASCT is no longer recommended in first remission. We here explored whether consolidative HDT/ASCT improved survival in defined subgroups of previously untreated patients. We report survival analyses of 431 patients who received frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for advanced FL, and were randomized to receive consolidative HDT/ASCT. We performed targeted genotyping of 157 diagnostic biopsies, and calculated genotype-based risk scores. HDT/ASCT improved failure-free survival (FFS; hazard ratio [HR], 0.8, P = .07; as-treated: HR, 0.7, P = .04), but not overall survival (OS; HR, 1.3, P = .27; as-treated: HR, 1.4, P = .13). High-risk cohorts identified by FL International Prognostic Index (FLIPI), and the clinicogenetic risk models m7-FLIPI and POD within 24 months-prognostic index (POD24-PI) comprised 27%, 18%, and 22% of patients. HDT/ASCT did not significantly prolong FFS in high-risk patients as defined by FLIPI (HR, 0.9; P = .56), m7-FLIPI (HR, 0.9; P = .91), and POD24-PI (HR, 0.8; P = .60). Similarly, OS was not significantly improved. Finally, we used a machine-learning approach to predict benefit from HDT/ASCT by genotypes. Patients predicted to benefit from HDT/ASCT had longer FFS with HDT/ASCT (HR, 0.4; P = .03), but OS did not reach statistical significance. Thus, consolidative HDT/ASCT after frontline R-CHOP did not improve OS in unselected FL patients and subgroups selected by genotype-based risk models.

View details for DOI 10.1182/bloodadvances.2020002546

View details for PubMedID 32941649